Abstract
Background & Aims: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. Methods: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). Results: Histologic improvement occurred in 55% (68/124) of entecavir-treated vs 28% (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55% (77/141) vs 4% (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log10 copies/mL for entecavir-treated patients and -0.48 log10 copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. Conclusions: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile.
| Original language | English |
|---|---|
| Pages (from-to) | 2039-2049 |
| Number of pages | 11 |
| Journal | Gastroenterology |
| Volume | 130 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Gastroenterology
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Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B. / Sherman, Morris; Yurdaydin, Cihan; Sollano, Jose; Silva, Marcelo; Liaw, Yun Fan; Cianciara, Janusz; Boron-Kaczmarska, Anna; Martin, Paul; Goodman, Zachary; Colonno, Richard; Cross, Anne; Denisky, Gail; Kreter, Bruce; Hindes, Robert.
In: Gastroenterology, Vol. 130, No. 7, 01.07.2006, p. 2039-2049.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B
AU - Sherman, Morris
AU - Yurdaydin, Cihan
AU - Sollano, Jose
AU - Silva, Marcelo
AU - Liaw, Yun Fan
AU - Cianciara, Janusz
AU - Boron-Kaczmarska, Anna
AU - Martin, Paul
AU - Goodman, Zachary
AU - Colonno, Richard
AU - Cross, Anne
AU - Denisky, Gail
AU - Kreter, Bruce
AU - Hindes, Robert
PY - 2006/7/1
Y1 - 2006/7/1
N2 - Background & Aims: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. Methods: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). Results: Histologic improvement occurred in 55% (68/124) of entecavir-treated vs 28% (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55% (77/141) vs 4% (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log10 copies/mL for entecavir-treated patients and -0.48 log10 copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. Conclusions: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile.
AB - Background & Aims: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. Methods: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). Results: Histologic improvement occurred in 55% (68/124) of entecavir-treated vs 28% (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55% (77/141) vs 4% (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log10 copies/mL for entecavir-treated patients and -0.48 log10 copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. Conclusions: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile.
UR - http://www.scopus.com/inward/record.url?scp=33744531146&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33744531146&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2006.04.007
DO - 10.1053/j.gastro.2006.04.007
M3 - Article
C2 - 16762627
AN - SCOPUS:33744531146
VL - 130
SP - 2039
EP - 2049
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 7
ER -